Sarcopenia
Encyclopedia
Sarcopenia is the degenerative loss of skeletal muscle
mass and strength associated with aging (0.5-1% loss per year after the age of 25). Sarcopenia is a component of the frailty syndrome
.
The European Working Group on Sarcopenia in Older People (EWGSOP) has developed a practical clinical definition and consensus diagnostic criteria for age-related sarcopenia. For the diagnosis of sarcopenia, the working group has proposed using the presence of both low muscle mass + low muscle function (strength or performance).
, which causes weakness and frailty. However, this loss of muscle mass may be caused by different cellular mechanisms than those that cause muscle atrophy
. For example, during sarcopenia, there is a replacement of muscle fibres with fat
and an increase in fibrosis
.
Lack of exercise is currently thought to be a significant risk factor, increasing the likelihood of sarcopenia.
Not only muscle but the entire musculoskeletal system of muscle, neuromuscular responsiveness, endocrine function, vasocapillary access, tendon, joint, ligament, and bone, depends on regular and lifelong exercise to maintain integrity. The slow attenuation, atrophy, or loss of muscle tissue that medical professionals sometimes describe as sarcopenia (literally, "flesh loss') is currently thought to be the result of cumulative loss of musculoskeletal strength and mass associated with chronic absence of exercise of sufficient intensity or volume. However, even highly trained athletes experience the effects of sarcopenia. It is interesting to note that athletic speed and strength records are generally set by individuals no older than 30 years of age, although some powerlifters and other strength athletes continue to set records into their 50s.
measurement does not provide enough data to determine whether or not an individual is suffering from severe sarcopenia. Sarcopenia is also marked by a decrease in the circumference of distinct types of muscle fibers. Skeletal muscle has different fiber-types, which are characterized by expression of distinct myosin
variants. During sarcopenia, there is a decrease in "type 2" fiber circumference (Type II), with little to no decrease in "type I" fiber circumference (Type I). However, we lose both type I and type II muscle fibers (muscle cells) equally as we age (contrary to popular belief that we lose type II more rapidly).
are small mononuclear cells that abut the muscle fiber. Satellite cells are normally activated upon injury or exercise. These cells then differentiate and fuse into the muscle fiber, helping to maintain its function. One theory is that sarcopenia, is in part caused by a failure in satellite cell activation.
Therefore, the ability to repair damaged muscles or respond to nutritional signals is impaired.
and testosterone
, and promotion of catabolic signals, such as pro-inflammatory cytokines.
of industrialized populations, sarcopenia is emerging as a major health concern. Sarcopenia may progress to the extent that an older person may lose his or her ability to live independently. Furthermore, sarcopenia is an important independent predictor of disability in population-based studies, linked to poor balance, gait speed, falls, and fractures. Sarcopenia can be thought of as a muscular analog of osteoporosis
, which is loss of bone, also caused by inactivity and counteracted by exercise. The combination of osteoporosis
and sarcopenia results in the significant frailty often seen in the elderly population.
world records of muscle-intensive sports, such as weight lifting.
(DEXA) compared to a normal reference population. His working definition uses a cut point of 2 standard deviations below the mean of lean mass for gender specific healthy young adults.
This methodology is attractive for definitive diagnosis in clinical settings as well for several reasons. Primarily, emerging research shows it is predictive of negative outcomes and it is also a method familiar to most clinicians. This later point is especially true for those that treat the geriatric population, given its similarity to the 1996 World Health Organization
(WHO) methodology for definitive diagnosis of osteoporosis
, which also uses DEXA, but uses a measure of lean mass rather than bone mineral density (BMD). DEXA is widely used already in clinical settings in developed countries to identify and monitor severity of osteoporosis. And the degree of sarcopenia can be measured using DEXA in patients being evaluated for osteoporosis, at the same time with the same scan, with no added cost or radiation exposure to the patient.
Since Baumgartner’s working definition first appeared, some consensus groups have refined the definition, including the recent joint effort of the European Society on Clinician Nutrition and Metabolism (ESPEN) Special Interest Groups (SIG) on geriatric nutrition and on cachexia-anorexia
in chronic wasting diseases. Their consensus definition is:
1) A low muscle mass, >2 standard deviations below that mean measured in young adults (aged 18–39 years in the 3rd NHANES population) of the same sex and ethnic background, and
2) Low gait speed (e.g. a walking speed below 0.8 m/s in the 4-m walking test).
However, it can be replaced by one of the well-established functional tests utilized locally as being part of the comprehensive geriatric assessment.
There remains many opportunities for further refinement of reference populations by ethnic groups, and to further correlate of the degrees of severity of sarcopenia to overt declines in functional performance (preferably using verified functional tests), as well as incidence of hospitalization admissions, morbidity and mortality. Work toward this objective has already begun, and the body of research to date clearly points toward severe sarcopenia is predicative of negative outcomes, similar to what already been shown to exist with the Frailty syndrome
, as defined by the criteria set forth in 2001 by Fried et al.
Other approved medications have been shown to have little to no effect in this setting, including agents such DHEA and human growth hormone.
New therapies in clinical development hold great promise in this area, including the Selective androgen receptor modulator
s (SARMs), as evidenced by recent studies. Nonsteriodal SARMs are of particular interest, given they exhibit significant selectivity between the anabolic effects of testosterone on muscle, but apparently with little to no androgenic effects such as prostate stimulation in men or virilization in women.
Skeletal muscle
Skeletal muscle is a form of striated muscle tissue existing under control of the somatic nervous system- i.e. it is voluntarily controlled. It is one of three major muscle types, the others being cardiac and smooth muscle...
mass and strength associated with aging (0.5-1% loss per year after the age of 25). Sarcopenia is a component of the frailty syndrome
Frailty syndrome
The frailty syndrome is a collection of symptoms or markers, primarily due to the aging-related loss and dysfunction of skeletal muscle and bone, that place older adults at increased risk of adverse events such as death, disability, and institutionalization.-Sarcopenia:Sarcopenia, refers to loss...
.
Definition of sarcopenia
At present, there is no generally accepted definition of sarcopenia in the medical literature.The European Working Group on Sarcopenia in Older People (EWGSOP) has developed a practical clinical definition and consensus diagnostic criteria for age-related sarcopenia. For the diagnosis of sarcopenia, the working group has proposed using the presence of both low muscle mass + low muscle function (strength or performance).
Markers of sarcopenia
Sarcopenia is characterized first by a decrease in the size of the muscleMuscle
Muscle is a contractile tissue of animals and is derived from the mesodermal layer of embryonic germ cells. Muscle cells contain contractile filaments that move past each other and change the size of the cell. They are classified as skeletal, cardiac, or smooth muscles. Their function is to...
, which causes weakness and frailty. However, this loss of muscle mass may be caused by different cellular mechanisms than those that cause muscle atrophy
Muscle atrophy
Muscle atrophy, or disuse atrophy, is defined as a decrease in the mass of the muscle; it can be a partial or complete wasting away of muscle. When a muscle atrophies, this leads to muscle weakness, since the ability to exert force is related to mass...
. For example, during sarcopenia, there is a replacement of muscle fibres with fat
Fat
Fats consist of a wide group of compounds that are generally soluble in organic solvents and generally insoluble in water. Chemically, fats are triglycerides, triesters of glycerol and any of several fatty acids. Fats may be either solid or liquid at room temperature, depending on their structure...
and an increase in fibrosis
Fibrosis
Fibrosis is the formation of excess fibrous connective tissue in an organ or tissue in a reparative or reactive process. This is as opposed to formation of fibrous tissue as a normal constituent of an organ or tissue...
.
Benefit of exercise
Exercise and increases in activity have been shown to be beneficial in settings of sarcopenia; exercise even in the very old can increase strength and muscle function.Lack of exercise is currently thought to be a significant risk factor, increasing the likelihood of sarcopenia.
Not only muscle but the entire musculoskeletal system of muscle, neuromuscular responsiveness, endocrine function, vasocapillary access, tendon, joint, ligament, and bone, depends on regular and lifelong exercise to maintain integrity. The slow attenuation, atrophy, or loss of muscle tissue that medical professionals sometimes describe as sarcopenia (literally, "flesh loss') is currently thought to be the result of cumulative loss of musculoskeletal strength and mass associated with chronic absence of exercise of sufficient intensity or volume. However, even highly trained athletes experience the effects of sarcopenia. It is interesting to note that athletic speed and strength records are generally set by individuals no older than 30 years of age, although some powerlifters and other strength athletes continue to set records into their 50s.
Fiber-type changes in sarcopenia
Simple circumferenceCircumference
The circumference is the distance around a closed curve. Circumference is a special perimeter.-Circumference of a circle:The circumference of a circle is the length around it....
measurement does not provide enough data to determine whether or not an individual is suffering from severe sarcopenia. Sarcopenia is also marked by a decrease in the circumference of distinct types of muscle fibers. Skeletal muscle has different fiber-types, which are characterized by expression of distinct myosin
Myosin
Myosins comprise a family of ATP-dependent motor proteins and are best known for their role in muscle contraction and their involvement in a wide range of other eukaryotic motility processes. They are responsible for actin-based motility. The term was originally used to describe a group of similar...
variants. During sarcopenia, there is a decrease in "type 2" fiber circumference (Type II), with little to no decrease in "type I" fiber circumference (Type I). However, we lose both type I and type II muscle fibers (muscle cells) equally as we age (contrary to popular belief that we lose type II more rapidly).
Loss of satellite cell function
Satellite cellsSatellite cells
Myosatellite cells or satellite cells are small mononuclear progenitor cells with virtually no cytoplasm found in mature muscle. They are found sandwiched between the basement membrane and sarcolemma of individual muscle fibers, and can be difficult to distinguish from the sub-sarcolemmal nuclei...
are small mononuclear cells that abut the muscle fiber. Satellite cells are normally activated upon injury or exercise. These cells then differentiate and fuse into the muscle fiber, helping to maintain its function. One theory is that sarcopenia, is in part caused by a failure in satellite cell activation.
Therefore, the ability to repair damaged muscles or respond to nutritional signals is impaired.
Loss of anabolic signals
Extreme muscle loss is often a result of both diminishing anabolic signals, such as growth hormoneGrowth hormone
Growth hormone is a peptide hormone that stimulates growth, cell reproduction and regeneration in humans and other animals. Growth hormone is a 191-amino acid, single-chain polypeptide that is synthesized, stored, and secreted by the somatotroph cells within the lateral wings of the anterior...
and testosterone
Testosterone
Testosterone is a steroid hormone from the androgen group and is found in mammals, reptiles, birds, and other vertebrates. In mammals, testosterone is primarily secreted in the testes of males and the ovaries of females, although small amounts are also secreted by the adrenal glands...
, and promotion of catabolic signals, such as pro-inflammatory cytokines.
Sarcopenia as a public-health problem
Due to the lessened physical activity and increased longevityLongevity
The word "longevity" is sometimes used as a synonym for "life expectancy" in demography or known as "long life", especially when it concerns someone or something lasting longer than expected ....
of industrialized populations, sarcopenia is emerging as a major health concern. Sarcopenia may progress to the extent that an older person may lose his or her ability to live independently. Furthermore, sarcopenia is an important independent predictor of disability in population-based studies, linked to poor balance, gait speed, falls, and fractures. Sarcopenia can be thought of as a muscular analog of osteoporosis
Osteoporosis
Osteoporosis is a disease of bones that leads to an increased risk of fracture. In osteoporosis the bone mineral density is reduced, bone microarchitecture is deteriorating, and the amount and variety of proteins in bone is altered...
, which is loss of bone, also caused by inactivity and counteracted by exercise. The combination of osteoporosis
Osteoporosis
Osteoporosis is a disease of bones that leads to an increased risk of fracture. In osteoporosis the bone mineral density is reduced, bone microarchitecture is deteriorating, and the amount and variety of proteins in bone is altered...
and sarcopenia results in the significant frailty often seen in the elderly population.
Natural history
Strength losses with ageing for men and women are relatively similar. They are greater for lower than upper extremity muscles. Maximum attainable strength peaks in mid-twenties and declines thereafter . The decline is precipitous after 65 years of age, though few longitudinal studies exist on this topic. A direct assessment of the effects of sarcopenia, even in extremely physically fit individuals, can be seen in the age-related decline in Masters athletics (track and field)Masters athletics (track and field)
Masters athletics is a class of the sport of athletics for veteran athletes in the events of track and field, road running and cross country running. The competitions feature five-year age groups beginning at age 35. Men as old as 104 and women in their 100s have competed in running, jumping and...
world records of muscle-intensive sports, such as weight lifting.
Diagnosis
Consensus on clinical diagnosis of sarcopenia has quickly developed over the last decade around the working definition proposed in 1998 by Baumgartner et al., which uses a measure of lean body mass as determined by Dual energy X-ray absorptiometryDual energy X-ray absorptiometry
Dual-emission X-ray absorptiometry is a means of measuring bone mineral density . Two X-ray beams with differing energy levels are aimed at the patient's bones. When soft tissue absorption is subtracted out, the BMD can be determined from the absorption of each beam by bone...
(DEXA) compared to a normal reference population. His working definition uses a cut point of 2 standard deviations below the mean of lean mass for gender specific healthy young adults.
This methodology is attractive for definitive diagnosis in clinical settings as well for several reasons. Primarily, emerging research shows it is predictive of negative outcomes and it is also a method familiar to most clinicians. This later point is especially true for those that treat the geriatric population, given its similarity to the 1996 World Health Organization
World Health Organization
The World Health Organization is a specialized agency of the United Nations that acts as a coordinating authority on international public health. Established on 7 April 1948, with headquarters in Geneva, Switzerland, the agency inherited the mandate and resources of its predecessor, the Health...
(WHO) methodology for definitive diagnosis of osteoporosis
Osteoporosis
Osteoporosis is a disease of bones that leads to an increased risk of fracture. In osteoporosis the bone mineral density is reduced, bone microarchitecture is deteriorating, and the amount and variety of proteins in bone is altered...
, which also uses DEXA, but uses a measure of lean mass rather than bone mineral density (BMD). DEXA is widely used already in clinical settings in developed countries to identify and monitor severity of osteoporosis. And the degree of sarcopenia can be measured using DEXA in patients being evaluated for osteoporosis, at the same time with the same scan, with no added cost or radiation exposure to the patient.
Since Baumgartner’s working definition first appeared, some consensus groups have refined the definition, including the recent joint effort of the European Society on Clinician Nutrition and Metabolism (ESPEN) Special Interest Groups (SIG) on geriatric nutrition and on cachexia-anorexia
Cachexia
Cachexia or wasting syndrome is loss of weight, muscle atrophy, fatigue, weakness, and significant loss of appetite in someone who is not actively trying to lose weight...
in chronic wasting diseases. Their consensus definition is:
1) A low muscle mass, >2 standard deviations below that mean measured in young adults (aged 18–39 years in the 3rd NHANES population) of the same sex and ethnic background, and
2) Low gait speed (e.g. a walking speed below 0.8 m/s in the 4-m walking test).
However, it can be replaced by one of the well-established functional tests utilized locally as being part of the comprehensive geriatric assessment.
There remains many opportunities for further refinement of reference populations by ethnic groups, and to further correlate of the degrees of severity of sarcopenia to overt declines in functional performance (preferably using verified functional tests), as well as incidence of hospitalization admissions, morbidity and mortality. Work toward this objective has already begun, and the body of research to date clearly points toward severe sarcopenia is predicative of negative outcomes, similar to what already been shown to exist with the Frailty syndrome
Frailty syndrome
The frailty syndrome is a collection of symptoms or markers, primarily due to the aging-related loss and dysfunction of skeletal muscle and bone, that place older adults at increased risk of adverse events such as death, disability, and institutionalization.-Sarcopenia:Sarcopenia, refers to loss...
, as defined by the criteria set forth in 2001 by Fried et al.
Exercise
Exercise has been considered of great interest in treatment of sarcopenia. There are several reports showing increased ability and capacity of skeletal muscle to synthesize proteins in response to short term resistance exercise . Also, it has been reported exercise can improve physical performance (strength and mobility) in elderly subjects. However, there is insufficient research demonstrating such findings in long term.Drugs
Possible therapeutic strategies include use of testosterone or anabolic steroids, though long term use of these agents is controversial in men given concerns of prostate symptoms, and essentially contraindicated in women, given concerns of virilization. Recent experimental results have shown testosterone treatments may induce adverse cardiovascular events.Other approved medications have been shown to have little to no effect in this setting, including agents such DHEA and human growth hormone.
New therapies in clinical development hold great promise in this area, including the Selective androgen receptor modulator
Selective androgen receptor modulator
Selective androgen receptor modulators or SARMs are a novel class of androgen receptor ligands. They are intended to have the same kind of effects as androgenic drugs like anabolic steroids but be much more selective in...
s (SARMs), as evidenced by recent studies. Nonsteriodal SARMs are of particular interest, given they exhibit significant selectivity between the anabolic effects of testosterone on muscle, but apparently with little to no androgenic effects such as prostate stimulation in men or virilization in women.